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Side Effects and AIs

Posted 4/29/2013

Posted in

  Rarely do I receive an email from one of my doctor colleagues with the suggestion that I share a particular study with you. This, however, is one of those rare moments. The study, from JCO, suggests that women who experience side effects (vaginal dryness, stiffness, etc) may have a lower recurrence rate than those who do not. The very big caveat is that this is a single study, and, especially if you are one of the rather rare women who does not have any side effects, do not be concerned.

  Here is the email from my colleague:

This study that showed that postmenopausal women taking tamoxifen or an aromastase inhibitor who had vasomotor symptoms (e.g., hot flashes), vaginal dryness or musckuloskeletal discomfort had less breast cancer recurrence and better survival. It might make women feel better about these annoying side effects and improve compliance.They can view the side effects like hair loss during chemotherapy: look how powerful these meds are against cancer!

One might argue that the symptoms simply indicate who actually took their medications, but in fact it reflects anyone who complained of this during the first year of therapy….so one might reason that those women who reported side effects would be less likely to then be compliant with their meds. There is another theory that the type of patient who does complain is actually the type who is is typically more compliant with meds…..who knows. The facts are the facts.

And here is the abstract and then a link to the study:

Specific Adverse Events Predict Survival Benefit in Patients

Treated With Tamoxifen or Aromatase Inhibitors: An

International Tamoxifen Exemestane Adjuvant

Multinational Trial Analysis



Duveken B.Y. Fontein, Caroline Seynaeve, Peyman Hadji, Elyse´e T.M. Hille, Willemien van de Water,


Hein Putter, Elma Meershoek-Klein Kranenbarg, Annette Hasenburg, Robert J. Paridaens,

Jean-Michel Vannetzel, Christos Markopoulos, Yasuo Hozumi, John M.S. Bartlett, Stephen E. Jones,

Daniel William Rea, Johan W.R. Nortier, and Cornelis J.H. van de Velde








Specific adverse events (AEs) associated with endocrine therapy and related to depletion or

blocking of circulating estrogens may be related to treatment efficacy. We investigated the

relationship between survival outcomes and specific AEs including vasomotor symptoms (VMSs) musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with breast cancer participating in the international Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial



Patients and Methods






Primary efficacy end points were disease-free survival (DFS), overall survival (OS), and distant


metastases (DM). VMSs, MSAEs, and VVSs arising in the first year of endocrine treatment were

considered. Patients who did not start or who discontinued their allocated therapy and/or had an

event (recurrence/death) within 1 year after randomization were excluded. Landmark analyses and

time-dependent multivariate Cox proportional hazards models assessed survival differences up to

5 years from the start of treatment.









A total of 9,325 patients were included. Patients with specific AEs (v nonspecific or no AEs) had


better DFS and OS (multivariate hazard ratio [HR] for DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866];

MSAEs, 0.826 [95% CI, 0.694 to 0.982]; VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for

OS: VMSs, 0.583 [95% CI, 0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570

[95% CI, 0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749

[95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not reporting these

symptoms. Increasing numbers of specific AEs were also associated with better survival

outcomes. Outcomes were unrelated to treatment allocation.









Certain specific AEs are associated with superior survival outcomes and may therefore be useful


in predicting treatment responses in patients with breast cancer treated with endocrine therapy.




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